Inhibitors of p38

A compound of the formula:

• wherein each of Q1 and Q2 are independently selected from a phenyl or 5-6 membered aromatic heterocyclic ring system, or a 8-10 membered bicyclic ring system of aromatic carbocyclic rings, aromatic heterocyclic rings or a combination of an aromatic carbocyclic ring and an aromatic heterocyclic ring;
• wherein the rings that make up Q1 are substituted with 1 to 4 substituents, each of which is independently selected from halo;
• C1-C3 alkyl optionally substituted with NR′2, OR′, CO2R′ or CONR′2;
• O—(C1-C3)-alkyl optionally substituted with NR′2, OR′, CO2R′ or CONR′2;
• NR′2;
• OCF3;
• CF3;
• NO2;
• CO2R′;
• CONHR′;
• SR′;
• S(O2)N(R′)2;
• SCF3;
• CN;
• N(R′)C(O)R4;
• N(R′)C(O)OR4;
• N(R′)C(O)C(O)R4;
• N(R′)S(O2)R4;
• N(R′)R4;
• N(R4)2;
• OR4;
• OC(O)R4;
• OP(O)3H2;
• N═CH—N(R′)2;
• 3,4-methylenedioxy;
• —NH—C(O)O—CH2-4-pyridine;
• —NH—C(O)CH2-morpholine;
• —NH—C(O)CH2-piperazine;
• or —NH—C(O)CH2-pyrrolidine;
• wherein the rings that make up Q2 are optionally substituted with up to 4 substituents, each of which is independently selected from halogen;
• C1-C3 straight or branched alkyl optionally substituted with R′, NR′2, OR′, CO2R′, S(O2)N(R′)2, N═CH—N(R′)2, R3, O—P(O3)H2, or CONR′2;
• O—(C1-C3)-alkyl;
• O—(C1-C3)-alkyl optionally substituted with NR′2, OR′, CO2R′, S(O2)N(R′)2, N═CR′—N(R′)2, R3, OP(O3)H2, or CONR′2;
• NR′2;
• OCF3;
• CF3;
• NO2;
• CO2R′;
• CONR′2;
• R3;
• OR3;
• NR32;
• SR3;
• C(O)R3;
• C(O)N(R′)R3;
• C(O)OR3;
• SR′;
• S(O2)N(R′)2;
• SCF3;
• N═CR′—N(R′)2;
• OR4;
• O—CO2R4;
• N(R′)C(O)R4;
• N(R′)C(O)OR4;
• N(R′)C(O)C(O)R4;
• N(R′)S(O2)R4;
• N(R′)R4;
• N(R4)2;
• OR4;
• OC(O)R4;
• OP(O)3H2;
• K;
• CN;
• —NH—C(═NH)—NH2;
• or —CH2—NH—C(═NH)—NH2;
• wherein each R′ is independently selected from hydrogen;
• (C1-C3)-alkyl;
• (C2-C3)-alkenyl or alkynyl;
• phenyl or phenyl substituted with 1 to 3 substituents independently selected from halo, methoxy, cyano, nitro, amino, hydroxy, methyl or ethyl;
• or a 5-6 membered heterocyclic ring system optionally substituted with 1 to 3 substituents independently selected from halo, methoxy, cyano, nitro, amino, hydroxy, methyl or ethyl;
• wherein each R is independently selected from hydrogen, —R2, —N(R2)2, —OR2, SR2, —C(O)—N(R2)2, —S(O2)—N(R2)2, —C(O)—OR2 or —C(O)R2 wherein two adjacent R are optionally bound to one another and, together with each Y to which they are respectively bound, form a 4-8 membered carbocyclic or heterocyclic ring;
• wherein each R2 is independently selected from hydrogen;
• or (C1-C3)-alkyl or (C2-C3)-alkenyl, each optionally substituted with —N(R′)2, —OR′, SR′, —O—C(O)—N(R′)2, —C(O)—N(R′)2, —S(O2)—N(R′)2, —C(O)—OR′, —NHSO2R4, —NHSO2R3, —C(O)N(R′)(R3), —NHC(O)R4, —N(R′)(R3), —N(R′)(R4), —C(O)R3, —C(O)N(R′)(R4), —N(R4)2, —C(O)N═C(NH)2 or R3;
• wherein each R3 is independently selected from 5-8 membered aromatic or non-aromatic carbocyclic or heterocyclic ring systems each optionally substituted with R′, R4, —C(O)R′, —C(O)R4, —C(O)OR4 or —K;
• or an 8-10 membered bicyclic ring system of aromatic carbocyclic rings, aromatic heterocyclic rings or a combination of an aromatic carbocyclic ring and an aromatic heterocyclic ring each optionally substituted with R′, R4, —C(O)R′, —C(O)R4, —C(O)OR4 or —K;
• wherein each R4 is independently selected from R′;
• (C1-C7)-straight or branched alkyl optionally substituted with R′, N(R′)2, OR′, CO2R′, CON(R′)2, SO2N(R′)2 or SO2N(R5)2;
• or a 5-6 membered carbocyclic or heterocyclic ring system optionally substituted with —N(R′)2, OR′, CO2R′, CON(R′)2, SO2N(R′)2 or SO2N(R5)2;
• wherein each R5 is independently selected from hydrogen, (C1-C3)-alkyl, or (C2-C3)-alkenyl;
• each optionally substituted with —N(R′)2, —OR′, SR′, —C(O)—N(R′)2, —S(O2)—N(R′)2, —C(O)—OR′, —NH—S(O2)(R′), —NHSO2R6, —C(O)N(R′)(R6), —NHC(O)R′, —N(R′)(R6), —C(O)R6, —C(O)N═C(NH)2 or R6;
• wherein each R6 is independently selected from 5-8 membered aromatic or non-aromatic carbocyclic or heterocyclic ring systems each optionally substituted with R′, —C(O)R′ or —C(O)OR′;
• or an 8-10 membered bicyclic ring system of aromatic carbocyclic rings, aromatic heterocyclic rings or a combination of an aromatic carbocyclic ring and an aromatic heterocyclic ring each optionally substituted with R′, —C(O)R′ or C(O)OR′;
• wherein each Y is independently selected from N or C, and wherein if either Y is N, then R or U attached to Y is a lone pair of electrons;
• wherein Z is CH, N, C(OCH3), C(CH3), C(NH2), C(OH) or C(F);
• wherein each U is independently selected from R or J;
• wherein each J is independently selected from a (C1-C4) straight chain or branched alkyl substituted with T;
• wherein each T is independently selected from either O(V) or N(H)(V);
• wherein each V is independently selected from C(O)N═C(R)(N(R)2), wherein the two geminal R on the nitrogen are optionally bound to one another to form a 4-8 membered carbocyclic or heterocyclic ring;
• wherein each K is independently selected from a (C1-C4) straight chain or branched alkyl substituted with D, or —OP(O)(OH)2;
• wherein each D is independently selected from either enantiomer of
• wherein each M is independently selected from either O or NH;
• wherein each G is independently selected from NH2, OH, or H;
• wherein each R8 is independently selected from H, OH, C(O)OH, (C1-C7)-straight or branched alkyl optionally substituted with N(R′)2, OR′, CO2R′, CON(R′)2, or SO2N(R5)2;
• or a 5-6 membered carbocyclic, heterocyclic or heteroaryl ring system optionally substituted with N(R′)2, OR′, CO2R′, CON(R′)2, or SO2N(R5)2;
• wherein G and R8 are optionally bound to one another to form a ring.